Expansion and length-dependent fragility of CTG repeats in yeast.
Expansion of DNA trinucleotide repeats (TNRs) is the causative mutation in a growing number of human genetic diseases. Large expansions of a CTG tract were obtained and shown by genetic and physical assays to be length-dependent sites of chromosome breakage in Saccharomyces cerevisiae. Deletion of RAD27, which encodes a nuclease involved in Okazaki fragment processing, caused length-dependent destabilization of CTG tracts and a substantial increase in expansion frequency. The genetic assay described here can be used to evaluate other factors that induce TNR expansion or chromosome fragility in humans.
Freudenreich
C H
CH
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Kantrow
S M
SM
Zakian
V A
VA
D019457:Chromosome Breakage; D002873:Chromosome Fragility; D015825:Chromosomes, Fungal / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004271:DNA, Fungal / Q000378:metabolism; D016521:Electrophoresis, Gel, Pulsed-Field; D043211:Exodeoxyribonuclease V; D005090:Exodeoxyribonucleases / Q000235:genetics; D017353:Gene Deletion; D005800:Genes, Fungal; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D014170:Transformation, Genetic; D019680:Trinucleotide Repeat Expansion; D018911:Trinucleotide Repeats / Q000235:genetics*
D004271:DNA, Fungal; D005090:Exodeoxyribonucleases; D043211:Exodeoxyribonuclease V; D006918:Hydroxyurea